Project Summary/Abstract Tobacco use is responsible for enormous health and financial costs in the U.S. including more than 480,000 deaths per year due to cigarette use and more than $193 billion annually in health care costs and loss of productivity. Sexual minority individuals are at substantially greater risk for tobacco use and tobacco use disorder (TUD) and tobacco-related health outcomes compared to heterosexual individuals in the U.S. Longitudinal data is needed to understand differences in tobacco use across time and resultant tobacco- related health disparities among sexual minorities. This information is necessary to inform tobacco regulatory policy strategies to reduce these health disparities. We draw on concepts of minority stress and intersectionality to understand these tobacco use trajectories and related health disparities by sexual orientation. This proposal is in direct response to RFA-OD-19-022 by using secondary data to examine tobacco use trajectories and its health effects over time in a vulnerable population, focusing on new tobacco products. The national and longitudinal Population Assessment of Tobacco and Health (PATH) study provides an unprecedented opportunity to identify differences in tobacco use trajectories, associated health disparities, and mechanisms behind these differences. Using PATH data we will be able to examine detailed tobacco use trajectories across four waves, sexual identity transitions across four waves, and prospective links to health outcomes. In addition we triangulate both self-report and biological data on stress and health. Using PATH?s large nationally representative dataset of youth and adults, this study aims to: (1) To examine tobacco product initiation and use trajectories by sexual orientation and their associations with regular tobacco use and TUD symptoms; (2) To identify tobacco use trajectories by sexual orientation and differential associations with self report and biological health outcomes among adults; (3) To examine the role of biological and psychological stress on tobacco use trajectories, tobacco cessation and tobacco-related health outcomes among adults and how this differs by sexual orientation and transitions in sexual identity. We will assess tobacco trajectories, with emphasis on specific changes of critical public health importance including: (1) tobacco use initiation, (2) progression in the number of tobacco products used (i.e., single product use to dual/polytobacco use) with a focus on trajectories including e-cigarettes and those without and (3) increases and decreases in tobacco frequency. Aims 2 and 3 will innovatively make use of the wealth of both survey self-report measures of stress (psychological distress) and health outcomes (respiratory illness, cancer, cardiovascular disease) alongside biological markers of stress (e.g., C-reactive protein, interleukin-6) and tobacco-specific markers linked to cancer risk (NNAL, NNN, TNE2). We will examine important moderators including age, sex, race, and ethnicity throughout all aims. This project will greatly inform and maximize effectiveness of tobacco regulatory policies particularly those aimed at reducing the health burden of tobacco use among sexual minorities.